Project Summary Millions of children in low- and middle-income countries (LMICs) struggle to reach their developmental potential. Early life exposures that are common in high-poverty settings, including undernutrition and chronic infection, contribute to cognitive deficits that have persistent effects into adulthood. The biological pathways that underlie the relationships between nutrition, inflammation, and cognitive development are complex and not entirely understood, in part due to measurement challenges in LMICs, where most undernutrition occurs. Characterizing these pathways is critical to inform the design of early interventions to promote global child health and cognitive development. This study will combine a novel dataset from an ongoing prospective cohort study in South Africa with collection of new data to examine the relationship of systemic inflammation with undernutrition and cognitive development. Whole blood samples to assess biomarkers of systemic inflammation will be collected during a lab visit already planned for the parent study. The study has two aims: 1) to examine the association of biomarkers of systemic inflammation (IL-1?, IL-6, and C-reactive protein) at 24 months of age with indicators of undernutrition, including low birthweight and repeated measures of stunting at 7 months, 15 months, and 24 months of age; and 2) to examine the relationship between biomarkers of systemic inflammation and two objective measures of cognitive development?EEG gamma power and saccadic reaction time?at 24 months of age. This study is significant because our results will strengthen understanding of the biological pathways affecting cognitive development in LMICs like South Africa. A growing body of evidence suggests that the negative impact of early adversity can be mitigated through appropriate early-life interventions. However, limitations in our current understanding of the root causes of deficits in cognitive development in LMICs are a barrier to developing more effective interventions. The new evidence this study generates will inform the future design of more effective interventions.